Background: The aim of this thesis was to study the relationship of pre-diagnostic circulating concentrations of sex steroid hormones (androgens, estradiol, 17-hydroxyprogesterone, and progesterone), growth factors (insulin-like growth factor-I (IGF-I), placental growth hormone (GH)), sex hormone binding globulin (SHBG), and anti-Müllerian hormone (AMH) with risk of epithelial ovarian cancer (EOC) overall, and by tumor invasiveness and histology. A longitudinal study was used to assess patterns of hormonal changes during a single pregnancy, and in two consecutive pregnancies. Materials & Methods: A case-control study was nested within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort. A total of 1 052 EOC cases were identified through linkages with the cancer registries in both countries. For each case, 2-3 controls were selected. Cases and controls were matched on cohort, age and date at blood draw, as well as for parity at blood draw and at diagnosis (n=2 695). Odds ratios (OR) and corresponding 95% confidence intervals [CI] were estimated using conditional logistic regression. The longitudinal study was based on 71 pregnant Finnish women, who donated blood samples in each trimester of pregnancy. Results: Higher androgen concentrations were associated with an increased risk of overall EOC (e.g., testosterone ORT3 vs. T1: 1.56 [1.30-1.87], ptrend<0.0001), while the risk of endometrioid tumors increased with higher estradiol concentrations (ORT3 vs. T1: 2.76 [1.04-7.33], ptrend=0.03). Higher IGF-I was associated with a non-significant decrease in risk for invasive (ORT3 vs. T1: 0.79 [0.62-1.02], ptrend=0.07) and endometrioid tumors (ORT3 vs. T1: 0.55 [0.28-1.07], ptrend=0.07). The inverse association between IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis (ORT3 vs. T1: 0.74 [0.57-0.96], ptrend=0.03). No associations were observed between pre-diagnostic progesterone, SHBG, placental GH, and AMH with EOC risk overall, or by tumor invasiveness and histology. The longitudinal study showed that hormone concentrations were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimesters. Further, 3rd trimester hormone concentrations can be estimated from 1st or 2nd trimester measurements. Conclusion: Higher pre-diagnostic androgens, estradiol, and IGF-I are associated with EOC risk, and associations differ by tumor invasiveness and histology.

Women seem to be largely protected against certain ‘welfare disorders’ such as cardiovacular disease and osteoporosis, during their fertile years.The metabolic changes observed during women’s non-menstrual states, i.e. during pregnancy, after the menopause and during use of oral contraceptives, indicate the importance of sex steroids and an undisturbed biological rhythm. Treatment with monophasic, combined oral contraceptives constitutes a model for the non-cyclic state.Growth hormone (GH) is a pituitary hormone that has major metabolic effects. The pattern of GH exposure to the target organ is of vital importance for the effects and changes in rhythm could possibly induce metabolic changes.Growth hormome, cholecystokinin (CCK), osteocalcin and angiotensinogen were used as markers for metabolic effects and the concentrations in serum were recorded in women during non-menstrual states. The clinical material comprised a total of 60 women: 18 healthy non-pregnant, 25 pregnant, one lactating woman and 16 postmenopausal women. Using a portable pump and a non-thrombogenic venous catheter, blood samples could be collected at 30-min intervals during 24-h periods. Furthermore, the effects of estrogen and GH in the regulation of angiotensinogen were investigated in an experimental model in the rat.Oral contraceptives were found to alter the secretion of GH towards a pattern of lower and more frequent peaks, though the total amount secreted during 24 h was unchanged. Oral contraceptives seem to induce a suppression of the 24-h concentrations of CCK, which may be important with respect to weight gain in some women. Osteocalcin in serum display a significant circadian variation. This emphasizes the need for careful timing of single point measurements and the value of continuous blood sampling. Oral contraceptives may reduce osteocalcin serum concentrations. The long-term effects on bone are unknown. During late pregnancy osteocalcin levels are extremely low, which could indicate osteoblast inhibition and reduced bone turnover. The mode of GH administration is important for the plasma concentration of angiotensinogen in the non-pregnant rat. Estrogen effects on this protein may be mediated via a modification of GH secretion. Oral contraceptives not only increase angiotensinogen concentrations in serum but also markedly enhance their variability. Further studies are needed to elucidate the relation between the individual pattern of angiotensinogen and hypertension. / <p>S. 1-42: sammanfattning, s. 43-88: 6 uppsatser</p> / digitalisering@umu

The developing chick retina is an extrapituitary site of growth hormone (GH) synthesis and action. GH, GH receptor (GHR) and their mRNAs are present in the neural retina when the neural cells are undergoing proliferation and differentiation during early embryogenesis. It is thus likely that GH acts as an autocrine or paracrine in this location. The present study shows that intra-vitreal injection of a chick GH (cGH) small interfering RNA (siRNA) into the eyes of early embryos [embryonic day (ED) 4] suppresses GH expression in the neural retina and increases the incidence of spontaneous retinal cell death. Our current work also demonstrates a reduction of local IGF-1 expression after retinal GH gene knockdown, suggesting that GH action in retinal cells is regulated through IGF-1 signalling. These results demonstrate that retinal GH is an autocrine/paracrine hormone that acts as a neuroprotective factor in the retina of chick embryos.

Submitted by MARILIA GABRIELA MALAVOLTA null (mariliamalavolta@yahoo.com.br) on 2016-06-27T13:23:11Z No. of bitstreams: 1 M. Malavolta Pinho -Tese - Estudos Lit. - 2016.pdf: 3213369 bytes, checksum: ae28473129bffa19f7ff653fe6a26ad7 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-06-27T13:59:40Z (GMT) No. of bitstreams: 1 pinho_mgm_dr_arafcl.pdf: 3213369 bytes, checksum: ae28473129bffa19f7ff653fe6a26ad7 (MD5) / Made available in DSpace on 2016-06-27T13:59:40Z (GMT). No. of bitstreams: 1 pinho_mgm_dr_arafcl.pdf: 3213369 bytes, checksum: ae28473129bffa19f7ff653fe6a26ad7 (MD5) Previous issue date: 2016-04-26 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O presente trabalho visa a propor que o ato narrativo de GH em A paixão segundo GH (1964), romance de Clarice Lispector, possui dimensão mística capaz de atestar uma apropriação intuitiva e estética, por parte da escritora, de prerrogativas do I Ching, o Livro das Mutações – grande repositório da cultura e sabedoria chinesas. Suas proposições argumentativas em torno deste eixo visam a incidir em espaços vazios (plenos de sentido) deixados pela crítica de Benedito Nunes. Com isto, espera-se que tais proposições agreguem novas possibilidades de leitura a alguns pontos levantados pelo acurado trabalho crítico empreendido por Nunes (dos quais aqui se destaca o pathos da escrita) e a metáforas ou códigos ficcionais empregados por Clarice, no que diz respeito, essencialmente, ao trabalho com a linguagem tal como empregado ou idealizado pela escritora frente à representação de uma realidade vivida, sentida ou intuída. Afluentes deste percurso são as imagens da Aderência aqui singularizada como um importante componente da poética clariciana. Confluentes deste percurso são as significativas relações diretas e indiretas, lineares e não lineares, em torno de Clarice Lispector, Benedito Nunes, a escrita ideogrâmica e o Clássico chinês das mutações. / The aim of this work is to propose that the narrative act of G.H. in Passion According to G.H. (1964), a novel by Clarice Lispector, features a mystical dimension which stands for the author’s intuitive and aesthetic appropriation of prerogatives found in I Ching, the Book of Changes – a great repository of Chinese culture and wisdom. The work’s argumentative proposition revolving around this core shall focus on empty spaces (full of meaning) left by Benedito Nunes’ criticism. As a result, it is expected that these propositions add new reading possibilities to some issues pointed out by the thorough critical work developed by Nunes (particularly the pathos of writing), as well as to metaphors and fictional codes used by Clarice, essentially regarding the work with language as used or devised by the writer in face of the representation of an experienced, felt or sensed reality. Contributions to this track are the images of Adherence singled out here as a major component of Lispectorian poetics. Convergences with this track are the significant direct and indirect, linear and non-linear relationships around Clarice Lispector, Benedito Nunes, ideogramic writing and the Chinese Classic of changes. / FAPESP: 2012/17156-0

Made available in DSpace on 2015-04-17T15:02:58Z (GMT). No. of bitstreams: 1 ArquivoTotalEdna.pdf: 984049 bytes, checksum: 117961fa58eb64aa291d84e674a97d38 (MD5) Previous issue date: 2013-07-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The aging process involves several physiological changes among them the decrease in anabolic hormones. As a result, more and more researches have been developed in order to improve the quality of life in this population. This research aimed to evaluate the effect of zinc supplementation on serum levels of GH, IGF-1 and IGFBP3 in elderly women. The study included 20 apparently healthy elderly and divided into 2 groups (Supplemented and Placebo). After approval by the Ethics Committee in Research of the Center for Health Sciences UFPB the elderly received 25mg/day of zinc or placebo for 90 days. The parameters were analyzed using the paired Student t test and unpaired GraphPad-Prism software v.5.04. We adopted a significance level of 5% for all tests. It was observed that the values of dietary zinc in both groups showed levels below recommended for the elderly, the control group showed a significant reduction in plasma zinc concentration from the beginning to the end of the experiment, while the supplemented group maintained levels plasma without significant changes in the same period. Zinc supplementation caused a significant increase in the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in both groups, but levels remained within the reference values. With regard to hormones zinc supplementation was able to increase the levels of GH and IGFBP3 (p = 0.004 and 0.02, respectively) and tended to increase IGF-1 levels (p = 0.06). It was observed that zinc supplementation produced an increase in serum levels of GH and IGFBP3 tendency to increase IGF-1. Therefore Zinc could be an alternative for increasing GH levels in the elderly without the harmful effects that GH replacement entails. / O processo de envelhecimento envolve várias alterações fisiológicas dentre elas a diminuição dos hormônios anabólicos. Em decorrência disso, cada vez mais pesquisas têm sido desenvolvidas com a finalidade de melhorar a qualidade de vida nessa população. Esta pesquisa teve como objetivo avaliar o efeito da suplementação de zinco sobre os níveis séricos de GH, IGF-1 e IGFBP3 em idosas. Foi desenvolvido um estudo clínico, randomizado, duplo cego com placebo controlado. Inicialmente foram selecionadas 56 idosas e após os critérios de exclusão participaram 20 idosas que foram divididas em 2 grupos: Zinco (n=10) e Placebo (n=10). Após a aprovação pelo Comitê de Ética em Pesquisa do Centro de Ciências da Sáude da UFPB as idosas receberam 25mg/dia de zinco ou placebo por 90 dias. Os parâmetros foram analisados por meio do teste t student no software GraphPad-Prism v.5.04. Adotou-se um nível de significância de 5% para todos os testes. Observou-se que os níveis de zinco dietético apresentaram-se abaixo do recomendado para os idosos no grupo zinco (5,7 ± 0,68 mg/dia ) e placebo (6,5 ± 0,66 mg/dia ). O grupo controle sofreu uma redução significativa na concentração de zinco plasmático do inicio até o final do experimento (1,0 ± 0,01 para 0,9 ± 0,02), enquanto que o grupo suplementado manteve os níveis plasmáticos sem alterações significativas neste mesmo período (1,0 ± 0,03 para 1,0 ± 0,04). As idosas de ambos os grupos apresentaram aumento das enzimas aspartato aminotransferase (AST) e alanina aminotransferase(ALT) após a suplementação, no entanto os níveis mantiveram-se dentro dos valores de referência. Com relação aos hormônios a suplementação de zinco foi capaz de aumentar os níveis de GH (p< 0,004) e IGFBP3 (p<0,02), embora o grupo zinco não tenha apresentado níveis hormonais melhores que o grupo placebo. O efeito do zinco foi superior ao do placebo, porém de pequena magnitude. Portanto, não podemos descartar a possibilidade do zinco ser uma alternativa para aumentar os níveis de GH em idosos, necessitando, portanto, a realização de outras pesquisas com um N maior.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-01-04T19:56:37Z No. of bitstreams: 1 ErikaDantasDeMedeirosRocha_TESE.pdf: 4403241 bytes, checksum: 64a54ee8bef97b88fcbc0956c52d05e2 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-01-05T20:15:47Z (GMT) No. of bitstreams: 1 ErikaDantasDeMedeirosRocha_TESE.pdf: 4403241 bytes, checksum: 64a54ee8bef97b88fcbc0956c52d05e2 (MD5) / Made available in DSpace on 2016-01-05T20:15:47Z (GMT). No. of bitstreams: 1 ErikaDantasDeMedeirosRocha_TESE.pdf: 4403241 bytes, checksum: 64a54ee8bef97b88fcbc0956c52d05e2 (MD5) Previous issue date: 2014-06-06 / Introdu??o: o zinco ? um importante micronutriente para numerosos processos bioqu?micos em animais e humanos, desempenhando papel de destaque no crescimento e desenvolvimento. Em popula??es mundiais, a defici?ncia prim?ria grave de zinco n?o ? comum, embora, a defici?ncia leve seja bastante prevalente. Considerando que o zinco ? essencial para a sa?de humana e regula o sistema hipot?lamo, hip?fise, f?gado e osso, buscamos averiguar os seus efeitos no eixo GH-IGF1-IGFBP3 agudamente, mediante administra??o intravenosa com o elemento zinco, e cronicamente, mediante suplementa??o oral com o elemento zinco, usando doses fisiol?gicas de 0.06537 mg Zn/kg (via intravenosa) e 10 mg Zn/dia (via oral). A inclus?o de crian?as pr?-p?beres aparentemente saud?veis e eutr?ficas sem defici?ncia de zinco ? raro na literatura, pois grande parte das publica??es foram reportadas em crian?as apresentando defici?ncia de zinco. A metodologia aplicada foi absolutamente inovadora e original, tornando o estudo altamente relevante para a interface entre endocrinologia e nutri??o. Objetivo: investigar os efeitos da suplementa??o oral e administra??o intravenosa com o elemento zinco sobre a secre??o de GH, IGF1, IGFBP3, OCN, ALP, TRAP e PT em crian?as aparentemente saud?veis e eutr?ficas sem defici?ncia de zinco. M?todos: o estudo foi conduzido durante um per?odo de tr?s meses, e caracterizado por ser randomizado controlado triplo cego. As crian?as foram selecionadas por amostragem n?o probabil?stica de conveni?ncia, provenientes de escolas p?blicas municipais, de ambos os g?neros, na faixa et?ria compreendida entre 8 e 9 anos de idade, divididas em grupo controle (20 crian?as recebendo solu??o placebo contendo 10% de sorbitol) e grupo experimental (20 crian?as suplementadas com o elemento zinco na forma de sulfato de zinco heptahidratado ? ZnSO4.7H2O). As crian?as foram submetidas ? suplementa??o oral de zinco elementar (10 mg Zn/dia) e ? administra??o intravenosa de zinco (0.06537 mg Zn/kg de peso corporal), na forma de ZnSO4.7H2O, cujas amostras sangu?neas foram coletadas em 0, 60, 120, 180 e 210 minutos. Foram realizadas avalia??es antropom?tricas e diet?ticas e dosagens bioqu?micas e hormonais nas crian?as estudadas. Resultados: ap?s a suplementa??o oral, foi observado no grupo experimental (i) aumento significativo dos valores de ingest?o de energia total, prote?na e gordura total (p = 0.0007, p< 0.0001, p< 0.0001, respectivamente), (ii) aumento significativo do zinco s?rico basal (p< 0.0001), aumento significativo das concentra??es plasm?ticas de fostatase alcalina (p = 0.0270), e (iv) correla??o positiva com o IGF1, IGFBP3, OCN, comparando antes e ap?s a suplementa??o (p = 0.0011, p< 0.0001, p< 0.0446, respectivamente). Durante a administra??o venosa de zinco, as concentra??es plasm?ticas de IGF1 e IGFBP3 aumentaram significativamente no grupo experimental (p = 0.0468, p < 0.0001, respectivamente). Em rela??o o c?lculo da adequa??o aparente, segundo as DRI, para o c?lcio, houve inadequa??o da dieta com 85% de confiabilidade dos dados; para o ferro, adequa??o da dieta, com 85% de confiabilidade dos dados. Para o zinco, adequa??o da dieta, com 50% de confiabilidade dos dados. Conclus?es: a suplementa??o oral com o elemento zinco pode ter estimulado um aumento na ingest?o de energia total, prote?na e gordura total, assim como, nas concentra??es basais de zinco s?rico e nas concentra??es plasm?ticas de fosfatase alcalina. A administra??o intravenosa de zinco aumentou as concentra??es s?ricas de zinco e as concentra??es plasm?ticas de GH, IGF1 e IGFBP3 no grupo experimental.

Tese (doutorado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2007. / Submitted by Natália Cristina Ramos dos Santos (nataliaguilera3@hotmail.com) on 2009-10-08T12:58:52Z No. of bitstreams: 1 Tese_Lucio.pdf: 514577 bytes, checksum: 6c28ad08b04414b87c861bded45506e3 (MD5) / Approved for entry into archive by Luanna Maia(luanna@bce.unb.br) on 2009-10-08T14:54:02Z (GMT) No. of bitstreams: 1 Tese_Lucio.pdf: 514577 bytes, checksum: 6c28ad08b04414b87c861bded45506e3 (MD5) / Made available in DSpace on 2009-10-08T14:54:02Z (GMT). No. of bitstreams: 1 Tese_Lucio.pdf: 514577 bytes, checksum: 6c28ad08b04414b87c861bded45506e3 (MD5) Previous issue date: 2007 / Contexto: A acromegalia é uma doença crônica que resulta da hipersecreção do hormônio do crescimento (GH) e do fator de crescimento insulina-símile I (IGF-I). Está associada à redução da expectativa de vida e a elevadas morbidade e mortalidade cardiovasculares cuja patogênese não está plenamente entendida. A acromegalia pode se acompanhar de uma miocardiopatia específica, caracterizada principalmente por hipertrofia do ventrículo esquerdo. Também estão freqüentemente presentes outros fatores de risco cardiovasculares, tais como, alteração do perfil lipídico (principalmente, hipertrigliceridemia, redução do colesterol HDL e incremento do número de partículas de LDL pequenas e densas) e aumento dos níveis séricos de lipoproteína(a)), diabetes melito e hipertensão. As complicações cardiovasculares respondem por 60% das mortes nos pacientes acromegálicos. Entretanto, o papel da aterosclerose na patogênese das complicações cardiovasculares da acromegalia ainda não está estabelecido. De fato, as alterações nos níveis séricos dos lípides e lipoproteínas descritas na acromegalia são inconsistentes e discordantes. Além disso, dados sobre os chamados fatores de risco cardiovascular emergentes ou não-clássicos (p.ex., proteína C reativa, homocisteína e fatores homeostáticos) são limitados e conflitantes. Objetivo: O objetivo principal deste estudo é avaliar em portadores de acromegalia a freqüência de fatores de risco cardiovascular metabólicos clássicos (níveis elevados do colesterol total, colesterol LDL, colesterol VLDL e triglicerídeos, diabetes melito e baixos valores do colesterol HDL) e não-clássicos (valores elevados de proteína C reativa ultrasensível, HOMA-IR, homocisteína, lipoproteína(a) e fibrinogênio, além de níveis baixos de antitrombina III, proteína C e proteína S). Pacientes e Métodos: Sessenta e dois pacientes acromegálicos (50 com acromegalia ativa e 12 com acromegalia controlada) e um grupo controle composto por 36 indivíduos saudáveis foram submetidos à dosagem dos lípides, glicemia de jejum, insulina (para determinação do índice HOMA-IR), lipoproteína(a), proteína C reativa ultra-sensível (PCRus), homocisteína e parâmetros primariamente relacionados à trombogênese (fibrinogênio, antitrombina III, proteína C e proteína S), bem como GH e IGF-I. Resultados: Comparados ao grupo controle, os pacientes com acromegalia ativa apresentaram valores significantemente mais elevados de glicemia de jejum (129,0 ± 53,7 vs. 88,9 ± 9,3; p =0,048), colesterol total (205,0 ± 46,5 vs. 179,5±29,4 mg/dL; p =0,010), colesterol LDL (127,1 ± 38,5 vs. 102,8 ± 27,0 mg/dL; p =0,004), colesterol VLDL (112,8 ± 22,2 vs. 22,5 ± 8,0 mg/dL; p <0,001), triglicerídeos (223,4 ± 107,4 vs. 110,9 ± 45,3 mg/dL; p <0,001), lipopoproteína(a) (85,1 ± 56,1 vs. 27,6 ± 32,1 mg/dL; p =0,023), fibrinogênio (434,8 ± 117,6 vs. 314,3 ± 65,8 mg/dL; p =0,008) e HOMA-IR (3,8 ± 2,6 vs. 1,6 ± 1,1; p =0,032), bem como níveis mais baixos de colesterol HDL (44,6 ± 9,9 vs. 55,6 ± 10,3 mg/dL; p <0,001) e proteína S (71,9 ± 24,7 vs. 99,6 ± 12,9%; p =0,041). Em ambos os grupos, os níveis de homocisteína, antitrombina III, proteína C e PCR-us foram similares. Além disso, pacientes com acromegalia ativa, em comparação àqueles com acromegalia controlada, apresentaram valores significativamente mais elevados de glicemia de jejum (129,0 ± 53,7 vs. 93,8 ± 11,1 mg/dL; p =0,048), HOMA-IR (3,8 ± 2,6 vs. 1,8 ± 1,0; p =0,032), fibrinogênio (434,8 ± 117,6 vs. 316,0 ± 78,9 mg/dL; p =0,008), colesterol VLDL (112,8 ± 22,2 vs. 44,2 ± 14,3 mg/dL; p <0,001) e lipoproteína(a) (85,1 ± 56,1 vs. 25,5 ± 15,8 mg/dL; p =0,023) porém níveis significativamente mais baixos de colesterol HDL (44,6 ± 9,9 vs. 45,3 ± 14,0 mg/dL; p < 0,001), proteína S (71,9 ± 24,7 vs. 78,5 ± 18,7%; p =0,041) e PCR-us (1,3 ± 1,6 vs. 3,9 ± 1,7 mg/L; p <0,001). Os seguintes fatores de risco foram significativamente mais comuns na acromegalia ativa do que na acromegalia controlada e no grupo controle: níveis baixos de colesterol HDL em homens (40,0% vs. 25,0% e 6,7%; p =0,048) e em mulheres (80,0% vs. 50,0% e 14,3%; p =0,044), níveis baixos de proteína S (44,0% vs. 18,0% e 0,0%; p =0,031), diabetes melito (16,0% vs. 8,3% e 0,0%; p =0,027), glicemia de jejum alterada (30,0% vs. 8,3% e 11,1%; p = 0,014), HOMA-IR >2,71 (36,0% vs. 16,7% e 11,1%; p =0,014), bem como valores elevados de colesterol VLDL (100,0% vs. 50,0% e 12,9%; p =0,041), triglicerídeos (56,0% vs. 33,3% e 22,2%; p =0,042) e lipoproteína(a) (66,0% vs. 30,0% e 27,7%; p =0,038). Adicionalmente, o risco cardiovascular, avaliado pelo escore de Framingham, foi significativamente maior nos portadores de acromegalia ativa do que naqueles com acromegalia controlada. Conclusão: Em comparação ao grupo controle e aos pacientes com acromegalia controlada, os pacientes com acromegalia ativa apresentaram uma freqüência de fatores de risco cardiovascular clássicos e não-clássicos significativamente maior. Esses achados reforçam a importância da normalização dos níveis de GH e IGF-I na redução das complicações cardiovasculares da acromegalia. _____________________________________________________________________________________ ABSTRACT / Context: Acromegaly is a chronic disease that results from growth hormone (GH) and insulin-like growth factor I (IGF-I) hypersecretion. It is associated with increased cardiovascular morbidity and mortality whose pathogenesis is not fully understood. Acromegaly is characterized by the association of a specific cardiomiopathy, mainly represented by concentric hypertrophy of the left ventricle. Other cardiovascular risk factors are also often present, such as altered lipid profile (in particular, low high-density lipoprotein (HDL)-cholesterol levels, hypertriglyceridemia and high small dense low-density lipoprotein (LDL)-cholesterol levels), high levels of lipoprotein(a) , diabetes mellitus and hypertension. Cardiovascular complications are responsible for 60% of deaths in acromegalic patients. However, the role of atherosclerosis in the pathogenesis of cardiovascular complications of acromegaly is not yet fully established. In fact, the changes in the concentrations of serum lipids and lipoproteins described in acromegaly have been rather inconsistent and discordant. Moreover, data on the so-called emerging or non-classical cardiovascular risk factors (for example, C-reactive protein, homocysteine and homeostatic factors) are limited and conflicting. Objective: The main objectif of this study was to evaluate in patients with acromegaly the prevalence of metabolic cardiovascular risk factors, both the classical ones (high levels of total cholesterol, LDL cholesterol, VLDL cholesterol and triglycerides, diabetes mellitus and low HDL cholesterol levels) and non-classical ones (high values of high sensitivity C-reactive protein, HOMA-IR, homocysteine, lipoprotein(a) and fibrinogen, as well as low levels of antithrombin III, protein C and protein S). Patients and Methods: Sixty-two acromegalic patients (50 with active acromegaly and 12 with controlled acromegaly) and a control group that included 36 healthy subjects were submitted to the measurement of lipids, fasting plasma glucose, insulin (to determine HOMAIR index), lipoprotein(a), high-sensitivity C-reactive protein (hsCRP), homocysteine and parameters primarily related to chrombogenesis (fibrinogen, antithrombin III, protein C and protein S), as well as GH and IGF-I levels. Results: Compared to control group, patients with active acromegaly presented with significantly higher values of fasting plasma glucose (129.0 ± 53.7 vs. 88.9 ± 9.3; p =0.048), total cholesterol (205.0 ± 46.5 vs. 179.5 ± 29.4 mg/dL; p =0.010), LDL cholesterol (127.1 ± 38.5 vs. 102.8 ± 27.0 mg/dL; p =0.004), VLDL cholesterol (112.8 ± 22.2 vs. 22.5 ± 8.0 mg/dL; p <0.001), triglycerides (223.4 ± 107.4 vs. 110.9 ± 45.3 mg/dL; p <0.001), lipopoprotein(a) (85.1 ± 56.1 vs. 27.6 ± 32.1 mg/dL; p =0.023), fibrinogen (434.8 ± 117.6 vs. 314.3 ± 65.8 mg/dL; p =0.008) and HOMA-IR (3.8 ± 2.6 vs. 1.6 ± 1.1; p =0.032), as well as lower levels of HDL cholesterol (44.6 ± 9.9 vs. 55.6 ± 10.3 mg/dL; p <0.001) and protein S (71.9 ± 24.7 vs. 99.6 ± 12.9%; p =0.041). In both groups, the levels of homocysteine, antithrombin III, protein C and hs-CRP were similar. Moreover, patients with active acromegaly, compared to those with controlled acromegaly, presented with significantly higher values of fasting plasma glucose (129.0 ± 53.7 vs. 93.8 ± 11.1 mg/dL; p =0.048), HOMA-IR (3.8 ± 2.6 vs. 1.8 ± 1.0; p =0.032), fibrinogen (434.8 ± 117.6 vs. 316.0 ± 78.9 mg/dL; p =0.008), VLDL cholesterol (112.8 ± 22.2 vs. 44.2 ± 14.3 mg/dL; p <0.001) and lipoprotein(a) (85.1 ± 56.1 vs. 25.5 ± 15.8 mg/dL; p =0.023) but with significantly lower levels of HDL cholesterol (44.6 ± 9.9 vs. 45.3 ± 14.0 mg/dL; p <0.001), protein S (71.9 ± 24.7 vs. 78.5 ± 18.7%; p =0.041) and hsCRP (1.3 ± 1.6 vs. 3.9 ± 1.7 mg/L; p <0.001). The following cardiovascular risk factors were significantly more common in active acromegaly than in controlled acromegaly and in the control group: low levels of HDL cholesterol in men (40.0% vs. 25.0% and 6.7%; p =0.048) and women (80.0% vs. 50.0% and 14.3%; p =0.044), low levels of protein S (44.0% vs. 18.0% and 0.0%; p =0.031), diabetes mellitus (16.0% vs. 8.3% and 0.0%; p =0.027), impaired fasting glycemia (30.0% vs. 8.3% and 11.1%; p =0.014), HOMA-IR >2.71 (36.0% vs. 16.7% and 11.1%; p =0.014), as well as high levels of VLDL cholesterol (100.0% vs. 50.0% and 12.9%; p =0.041), triglycerides (56.0% vs. 33.3% and 22.2%; p =0.042) and lipoprotein(a) (66.0% vs. 30.0% and 27.7%; p = 0.038). Furthermore, the cardiovascular risk, evaluated through the Framingham score, was significantly higher in patients with active acromegaly than in those with controlled acromegaly. Conclusion: Compared to the control group and patients with controlled acromegaly, patients with active acromegaly had a significantly higher frequency of classical and nonclassical cardiovascular risk factors. These findings highlight the importance of the normalization of GH and IGF-I levels in order to reduce cardiovascular complications of acromegaly.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

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